The proposed research stems from our previous demonstration that alfalfa meal, as well as an extract of alfalfa meal operationally termed alfalfa saponins, reduces the intestinal absorption of cholesterol, lowers cholesterolemia, and induces the regression of atherosclerosis in cholesterol-fed monkeys. However, because alfalfa saponins are a mixture of substances whose chemical structures are largely unknown, I have synthesized a series of novel saponins, i.e., cellobiose-tigogenin, cellobiose-diosgenin, glucose-diosgenin, and glucose-tigogenin. Preliminary experiments demonstrate that these saponins bind cholesterol in vitro. Other preliminary experiments showed that the first three of these also reduced intestinal absorption of cholesterol in rats. Not all members of the series have been tested yet. In the proposed research, certain synthetic saponins will be given to rats, rabbits, and monkeys. The effects of the saponins on the intestinal absorption of cholesterol will be further studied in rats, and a dose-response curve will be established. The possible absorption of the 14C-saponins will be determined. The mechanism of action of the synthetic saponins will be established through the steroid and bile acid balance technique. The effects of a 6-month period of ingesting survival, body growth rate, multiple hematologic and blood biochemical values, urinalysis results, and gross and microscopic pathological data. The effects of synthetic saponins on atherosclerosis prevention will be studied in rabbits with atheroscelerosis induced by a cholesterol diet or by a cholesterol-free diet. Finally, the effects of the synthetic saponins on cholesterolemia in monkeys will be studied. If the saponins reduce cholesterolemia without toxic effects, they might be used in the treatment of hypercholesterolemic humans.